Biphasic effects of anandamide.
Effects of the endogenous cannabimimetic anandamide were assessed over a wide dose range in a series of physiological and behavioral assays. These included the tetrad of tests in mice commonly used to assess cannabinoid-induced effects (motor activity, ring catalepsy, hypothermia, and analgesia tests), as well as a model for agonistic behavior on dyadic interactions of singly housed males with nonaggressive group-housed partners. Anandamide-induced effects on leukocyte phagocytosis were measured in a chemiluminescence assay. Results indicated that the higher doses tested (10-100 mg/kg) produced the well-known inhibitory effects in all of the above parameters as well as inhibition of phagocytosis. The lowest dose of anandamide tested (0.01 mg/kg) stimulated behavioral activities in the open field, on the ring and aggressive behavior in timid singly housed mice. This dose of 0.01 mg/kg, also stimulated phagocytosis. We suggest several possible mechanisms to explain these findings such as a differential involvement of a Gs and a Gi protein activated at low and high doses, respectively, allosteric modulation of the cannabinoid, and activation of presynaptic cannabinoid receptors by low doses of anandamide.
Sulcova
E
E
Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Mechoulam
R
R
Fride
E
E
D000374:Aggression / Q000187:drug effects; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced; D003672:Defecation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D005260:Female; D007962:Leukocytes / Q000187:drug effects; D008163:Luminescent Measurements; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D053284:Polyunsaturated Alkamides
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C078814:anandamide